Anatomía Comparada del Bazo de la Rata Blanca (Rattus norvegicus albinus), Una Revisión de la Literatura / Comparative Anatomy of the Spleen of the White Rat, (Rattus norvegicus albinus) a Literature Review

El bazo es el órgano linfático intraperitoneal más grande del organismo, presentando dos funciones principales: defensiva, mediante respuesta inmunitaria y filtración sanguínea. El objetivo de la presente revisión, fue obtener información actualizada sobre la anatomía del bazo de la rata albina (Rattus norvegicus albinus) y comparativa con la anatomía del bazo humano, perro, gato y cerdo, al representar las principales especies de importancia en la medicina, medicina veterinaria y en las ciencias biomédicas. Se realizó una búsqueda de material bibliográfico actualizado en diferentes sitios web científicos. Es así como, se revisaron 71 fuentes bibliográficas, en su gran mayoría artículos científicos (31), libros de anatomía humana y veterinaria (17), artículos especializados (17) y tesis (6). En general existe consenso, sobre la descripción anatómica del bazo, el cual se sitúa en la región hipocondriaca izquierda del abdomen, entre el fondo del estómago y el diafragma, irrigado por la arteria y vena esplénica. Se evidenció que existen similitudes en aspectos macroscópicos, al comparar el bazo de la rata blanca, con el bazo de otras especies (funcionalidad, peso relativo, ubicación topográfica). En aspectos microscópicos, el bazo en humanos y otros mamíferos se compone de estroma, además de parénquima, constituido a su vez por pulpa blanca y roja. En particular, existen diferencias entre el bazo de rata, humano, gato, perro y cerdo, en formas, tamaños y aspectos microscópicos, relacionados con la microcirculación e inmunidad. Mientras que existen semejanzas en procesos patológicos y respuestas a tratamientos farmacológicos y clínicos. Por lo anteriormente expuesto, se concluye que la rata albina constituye un buen modelo biológico, específicamente en aspectos anatómicos microscópicos del bazo de tipo inmunológico. Mientras que el bazo de cerdo es mejor comparativamente, en estudios anatómicos macroscópicos de tipo quirúrgicos, resultando ambos extrapolables, especialmente a la medicina humana.

SUMMARY: The spleen is the largest intraperitoneal lymphatic organ of the body, presenting two main functions: defensive, through immune response and blood filtration. The objective of the present review was to obtain updated information on the anatomy of the spleen of the albino rat (Rattus norvegicus albinus) and to compare it with the anatomy of the human, dog, cat and pig spleen, representing the main species of importance in medicine, veterinary medicine and biomedical sciences. A search for updated bibliographic material was carried out in different scientific websites. Thus, 71 bibliographic sources were reviewed, mostly scientific articles (31), human and veterinary anatomy books (17), specialized articles (17) and theses (6). In general, there is consensus on the anatomical description of the spleen, which is located in the left hypochondriac region of the abdomen between the fundus of the stomach and the diaphragm, irrigated by the splenic artery and vein. It was evidenced that there are similarities in macroscopic aspects when comparing the spleen of the white rat with the spleen of other species (functionality, relative weight, topographic location). In microscopic aspects, the spleen in humans and other mammals is composed of stroma, in addition to parenchyma, constituted in turn by white and red pulp. In particular, there are differences between rat, human, cat, dog and pig spleens in shapes, sizes and microscopic aspects related to microcirculation and immunity. While there are similarities in pathological processes and responses to pharmacological and clinical treatments. For the above mentioned, it is concluded that the albino rat constitutes a good biological model, specifically in microscopic anatomical aspects of the spleen of immunological type. While the pig spleen is comparatively better in macroscopic anatomical studies of surgical type, both are extrapolable especially to human medicine.

La función de las proteínas de choque térmico en las infecciones virales / The Role of Heat Shock Proteins in Viral Infections

Resumen Las proteínas de choque térmico se describieron como una respuesta intracelular al estrés calórico; sin embargo, al paso del tiempo, se observó que estas proteínas tienen múltiples funciones y que participan de manera relevante tanto en los procesos fisiológicos como patológicos. Las actividades que realizan las proteínas de choque térmico se relacionan con su localización, que puede ser intra o extracelular, al momento fisiológico y a las diferentes asociaciones estructurales, que pueden ser desde péptidos derivados de estas, hasta dímeros o multímeros. Con base en estas características funcionales, se les ha denominado proteínas multiempleo o "moonlighting proteins". En este artículo se describen algunas de las actividades de estas proteínas con relación al sistema inmunológico y las infecciones virales, en particular con los procesos inflamatorios.

Abstract Heat shock proteins (HSP) were first described as a cell response to heat stress. However, over time, it has become clear they have multiple functions inside and outside cells, and that they actively participate in different physiological and pathological processes. They perform functions related to their cellular location or physiological moment, which is why they have been called multi-use proteins or "moonlighting proteins". Furthermore, HSP activity is associated with different structural conformations, from peptides derived from them or as dimers or multimers, to mention a few. This article describes these functions and their relationship with the immune system, and their relationship with viral infection, particularly with inflammatory processes.

Alcohol: Immunomodulatory Effects and Cancer

ABSTRACT Alcohol consumption has been linked to numerous pathologic conditions, including infectious diseases and several types of cancer. Alcohol exerts its modulatory effects on the immune system (IS) in a dose- and time-dependent manner. Numerous studies indicate that these alterations affect responses such as peripheral inflammation or decreased antibody production and promote chronic inflammation, leading to cell death. The molecular mechanisms underlying these effects involve generating an oxidative tissue environment, producing cell damage-associated molecular patterns (DAMPs), and activating pattern recognition receptors. In particular, toll-like receptors and their signaling system emerge as central elements whose activity is altered by alcohol intake. There is also some epidemiological evidence demonstrating the causal role of alcohol in the development of various types of cancer, such as head-and-neck cancer, esophageal cancer, colorectal cancer, liver cancer, and breast cancer. Most recent evidence suggests that factors related to alcohol consumption and cancer include increased levels of acetaldehyde, production of reactive oxygen species, alteration in DNA methylation, and modifications in retinoid metabolism. In addition, changes associated with alcohol use on the IS and intestinal microbiota may favor the growth of some types of tumors.

Obesidad: un factor de riesgo en pacientes con COVID-19

Informes recientes dan cuenta de una fuerte asociación entre la obesidad y la severidad de la infección de COVID-19, lo cual se fundamenta en la presencia de un estado proinflamatorio crónico en el paciente obeso, vinculado a trastornos metabólicos y del sistema inmune. Este trabajo tiene como objetivo revisar los más recientes estudios sobre la asociación positiva que se establece entre la obesidad, como factor de riesgo, y la severidad y mortalidad de los pacientes con COVID-19; también renovar los mecanismos involucrados, para lo cual se seleccionaron artículos publicados -principalmente en los últimos cinco años- en las bases de datos PubMed, SciELO, ClinicalKey y LILACS, y en el motor de búsqueda Google Académico. Estos estudios incluyeron, entre otros parámetros, el Índice de Masa Corporal y su asociación a la severidad y mortalidad por COVID-19. Como resultado, la evidencia clínica sugiere que el sobrepeso y la obesidad presentan una alta prevalencia en los casos severos de pacientes adultos con COVID-19. Se concluye que la obesidad, en estos pacientes, requiere de un manejo particular, pues debe ser considerada un factor de riesgo independiente de otras comorbilidades. Esto se debe a su contribución a una mayor susceptibilidad y severidad, asociándose positivamente con alteraciones del sistema inmune y con reacciones hiperinflamatorias por liberación excesiva de citoquinas, comprometiendo el funcionamiento de órganos y sistemas y potenciando las complicaciones de la infección de SARS-CoV-2 y la mortalidad.

Recent reports indicate a strong association between obesity and the severity of COVID-19 infection, which is based on the presence of a chronic pro-inflammatory state in obese patients, linked to metabolic and immune system disorders. This paper aims to reviewing the most recent studies on the positive association established between obesity, as a risk factor, and severity and mortality of patients with COVID-19; it also aims to renew the involved mechanisms, for which articles published-mainly in the last five years-in the PubMed, SciELO, Clinical Key and LILACS databases, and in the Google Scholar search engine were selected. These studies included, among other parameters, the body mass index and its association to severity and mortality due to COVID-19. As a result, the clinical evidence suggests that overweight and obesity have a high prevalence in severe cases of adult patients with COVID-19. It is concluded that obesity, in these patients, requires a particular management, as it should be considered a risk factor independent of other comorbidities. This is due to its contribution to a greater susceptibility and severity, positively associated to alterations of the immune system and to hyper-inflammatory reactions by excessive release of cytokines, compromising the functioning of organs and systems and enhancing the complications of SARS-CoV-2 infection and mortality.

Papel de la plasticidad celular en la regeneración intestinalinducida por lesiones / Role of cell plasticity in injury-induced intestinal regeneration

El sistema intestinal posee una capacidad regenerativa intrínseca y fisiológica que tiene lugar a partir de las células madreLgr5+ ubicadas en el fondo de las criptas intestinales, las cuales se diferencian hacia las células progenitoras secretoras y absortivas con sus respectivas células especializadas mediante la activación de señalizaciones intracelulares como Wnt, Hippo y Notch. Condiciones adversas como lesiones e infecciones tisulares inducen esta actividad regenerativa promovida por variados mecanismos que influyen en el microambiente celular. El sistema inmunológico detecta alteraciones en el tejido intestinal y, a través de la activación de células inmunocompetentes y la secreción de citoquinas proinflamatorias, favorece la desdiferenciación de células especializadas hacia células madre para desencadenar la respuesta regenerativa. En cuanto al sistema nervioso entérico, su influencia está sujeta a modificaciones en la microbiota y los hábitos alimenticios, y se encuentra determinada en gran parte, por las células gliales entéricas y la expresión de distintos marcadores de plasticidad, que permiten limitar la lesión y reparar el tejido. Por su parte, la epigenéticamodifica la expresión genética y consecuentemente, la capacidadregenerativa intestinal, variando de acuerdo a cada paciente porla influencia de factores externos como la dieta o el estadopsicobiológico. De esta forma, la respuesta regenerativa intestinalinducida por lesiones, integra múltiples mecanismos y poseeimportantes repercusiones clínicas en cuanto a EII, disbiosise incluso tumorogénesis; conocer los mecanismos que regulanesta actividad puede sentar las bases para la creación de terapias innovadoras en el mismo ámbito(AU)

The intestinal system has an intrinsic and physiological regenerative capacity that takes place from the Lgr5+ stem cells located at the bottom of the intestinal crypts, which differentiate into secretory and absorptive progenitor cells with their specialized cells by activating intracellular signalslike Wnt, Hippo and Notch. Adverse conditions such asinjuries and tissue infections induce this regenerative activity promoted by various mechanisms that influence the cellular microenvironment. The immune system senses disturbances in the intestinal tissue and, through the activation of immunocompetent cells and the secretion of proinflammatorycytokines, favors the dedifferentiation of specialized cells intostem cells to trigger the regenerative response. Regarding theenteric nervous system, its influence is subject to modificationsin the microbiota and dietary habits, and is largely determinedby enteric glial cells and the expression of different plasticitymarkers, which enable to limit injuries and repair tissue. On the other hand, epigenetics modifies genetic expressionand, consequently, intestinal regenerative capacity, varying according to each patient due to the influence of external factors such as diet or psychobiological status. There fore, the intestinal regenerative response induced by lesions integrates multiple mechanisms and has important clinical repercussions in terms of IBD, dysbiosis, and even tumorigenesis; knowing themechanisms that regulate this activity can lay the foundations for the creation of innovative therapies in the same field (AU)

Myasthenia gravis in the complex scenario of LRBA-related immune dysregulation / Miastenia gravis no cenário clínico complexo das imunodesregulações relacionadas ao gene LRBA

Autoimmune diseases have been progressively recognized as a potential complication of primary immunodeficiency, especially for some genetic subtypes of common variable immunodeficiency. Although often associated with other autoimmune disorders, autoimmune myasthenia gravis is occasionally identified as a neuromuscular complication of primary immunodeficiency. We report the case of a Brazilian woman with common variable immunodeficiency-8 due to an LRBA variant, in which myasthenia gravis was identified in association with anti-acetylcholine receptor antibody. Marked clinical improvement occurred after intravenous immunoglobulin therapy.

Doenças autoimunes foram progressivamente reconhecidas como complicações potenciais das imunodeficiências primárias, especialmente para alguns subtipos genéticos das imunodeficiências comuns variáveis. Embora se associe comumente a outras doenças autoimunes, a Miastenia gravis autoimune adquirida foi raramente associada como complicação neuromuscular de imunodeficiências primárias. É descrito neste artigo o caso de paciente brasileira do sexo feminino com diagnóstico de Imunodeficiência Comum Variável tipo 8 por variante no gene LRBA, na qual foi identificada Miastenia gravis em associação a anticorpos antirreceptor de acetilcolina. Ela evoluiu com marcante melhora clínica após a introdução de terapêutica com imunoglobulina endovenosa.

Recomendaciones para el cuidado, prevención de infecciones y quimioprofilaxis en los errores innatos de la inmunidad / Recommendations for care, prevention of infections and chemoprophylaxis in inborn errors of immunity

Los errores innatos de la inmunidad (EII), antes llamados inmunodeficiencias primarias (IDP), son un grupo heterogéneo de trastornos genéticos con defectos en uno o más componentes del sistema inmune. Los pacientes afectados por EII presentan aumentada susceptibilidad a microorganismos únicos o múltiples que se manifestará con infecciones recurrentes de diferente tipo y gravedad dependiendo del tipo de la localización del defecto. La prevención de infecciones es uno de los pilares fundamentales en el abordaje integral de los pacientes con EII. En este trabajo se resumen las conclusiones consensuadas en el Grupo de Trabajo de Inmunología Pediátrica de la Sociedad Argentina de Pediatría, sobre la base de la revisión de la evidencia disponible, respecto a los principios esenciales para el cuidado, la prevención de infecciones y la quimioprofilaxis en los errores innatos de la inmunidad para la orientación del pediatra y especialista dedicados al seguimiento de estas enfermedades.

Inborn errors of immunity, previously named primary immunodeficiency are a heterogeneous group of genetic defects of different components of the immune system. Patients present high susceptibility to an only or several microorganisms, developing recurrent infections; the severity is related to the specific genetic type of immunity defect. The main strategy on the management of these illness is the prevention of infections. These consensus guidelines made by the Pediatric Immunology Work Group of Sociedad Argentina de Pediatría, givese main approaches of infection prevention in order to provide a useful tool for all practitioners who are involved in the management of these patients, based on scientific evidence and broad consensus of a specialized panel expert.

Effect of T-lymphocyte and subpopulation counts on the prognosis of patients with severe acute pancreatitis / 中华胰腺病杂志

Objective:To investigate the effect of T-lymphocyte and subpopulation counts on the prognosis of severe acute pancreatitis (SAP) patients.Methods:The clinical data of 90 patients with SAP diagnosed at the Shanghai General Hospital between January 2019 and June 2022 were retrospectively analyzed, and the patients were divided into good prognosis and poor prognosis group according to whether they were diagnosed for 28 d. The general information of the patients was recorded, including blood-related immunological indicators within 24 h of diagnosis, including leukocytes, neutrophils, lymphocytes, monocytes, CD 3+ , CD 4+ , CD 8+ T-lymphocyte count and CD 4+ /CD 8+ T-lymphocyte ratio, IgG4 level; blood inflammation index procalcitonin, albumin level and APACHEⅡ score at admission; survival and complication status of patients at 28 d of diagnosis. Non-parametric Mann-Whitney U test was used to analyze the correlation between each index and the prognosis of the patients. The subject operating characteristic curve (ROC) of patients was plotted, and area under curve (AUC) was calculated to assess the value of CD 3+ and CD 4+ T-lymphocytes in predicting the prognosis of SAP. Results:The majority of SAP patients were male (65.6%). The main cause of SAP was gallstone (56.7%), followed by hyperlipidemia (35.6%). At 28 days after diagnosis, 85(94.4%) patients survived, and 39 of them were cured and included in the good prognosis group. Forty-six cases were complicated with infection, multiple organ dysfunction syndrome (MODS) and local pancreatic complications, and 5 cases (5.56%) died; and a total of 51 cases were included in the poor prognosis group. Compared with the good prognosis group, the number of CD 3+ T-lymphocytes [366(268, 498) cells /μl vs 709(578, 999) cells /μl], CD 4+ T-lymphocytes [209(120, 298) cells /μl vs 486(303, 548) cells /μl] and albumin level (33.9 g/L vs 35.9 g/L) within 24 hours in the poor prognosis group were significantly lower, while the level of procalcitonin (1.02 ng/ml vs 0.43 ng/ml) and APACHEⅡ score [7(4, 10) vs 5(3, 8)] were significantly increased, and all the differences were statistically significant (all P value <0.05). ROC curve analysis showed that the AUC values for CD 3+ and CD 4+ T-lymphocyte counts within 24 hours for predicting poor prognosis of SAP were 0.857 (95% CI 0.696-1.000) and 0.867 (95% CI 0.708-1.000), respectively. The cut-off values were 524 cells /μl and 301 cells /μl, the sensitivity were both 85.7%, and the specificity were 78.6% and 85.7%, respectively. Conclusions:The significant decrease of peripheral blood CD 3+ and CD 4+ T-lymphocyte count within 24 h of SAP diagnosis has a certain predictive value for the prognosis of patients with SAP.

Effects of Delay in Tumor-Immune System on Stability / 医用生物力学

Objective To study stability of the deterministic tumor-immune system with time delay by means of linear stability analysis method. Methods In tumor-immune system, since it took some time for immune cells to recognize tumor cells and respond appropriately, time delay was considered in this process, then the model was simplified by using Taylor expansion of small delay, and the equilibrium points were solved out. By linear stability analysis method, the stability of these equilibrium points was studied. Finally, the trajectory of the system and that around each equilibrium point were simulated by numerical calculation method, so as to verify the result of theoretical analysis. Results The system had four meaningful equilibrium points with small delay, including a stable focus, a stable node, and two saddles. Moreover, the type and stability of these equilibrium points were not affected by the delay. Numerical simulation demonstrated the conclusion from theoretical analysis. Conclusions Under the condition of small delay, the type and stability of equilibrium points in the system are notaffected by the delay. The results are helpful to further understand dynamic mechanisms of tumor immune response, and provide references for tumor growth and treatment

Recent progress in application of nanovaccines for enhancing mucosal immune responses

Mucosal vaccines that stimulate both mucosal and systemic immune responses are desirable, as they could prevent the invading pathogens at their initial infection sites in a convenient and user-friendly way. Nanovaccines are receiving increasing attention for mucosal vaccination due to their merits in overcoming mucosal immune barriers and in enhancing immunogenicity of the encapsulated antigens. Herein, we summarized several nanovaccine strategies that have been reported for enhancing mucosal immune responses, including designing nanovaccines that have superior mucoadhesion and mucus penetration capacity, designing nanovaccines with better targeting efficiency to M cells or antigen-presenting cells, and co-delivering adjuvants by using nanovaccines. The reported applications of mucosal nanovaccines were also briefly discussed, including prevention of infectious diseases, and treatment of tumors and autoimmune diseases. Future research progresses in mucosal nanovaccines may promote the clinical translation and application of mucosal vaccines.

Immune cell membrane-based biomimetic nanomedicine for treating cancer metastasis

Metastasis is the leading cause of cancer-related death. Despite extensive treatment, the prognosis for patients with metastatic cancer remains poor. In addition to conventional surgical resection, radiotherapy, immunotherapy, chemotherapy, and targeted therapy, various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target effects. However, nanomedicines exhibit certain limitations in clinical applications, such as rapid clearance from the body, low biological stability, and poor targeting ability. Biomimetic methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these limitations. Considering the involvement of immune cells in the tumor microenvironment of the metastatic cascade, biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high biocompatibility. In this review, we explore the impact of immune cells on various processes of tumor metastasis. Furthermore, we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion, prolonged circulation, enhanced tumor accumulation, and immunosuppression of the tumor microenvironment. Moreover, we describe the prospects and existing challenges in clinical translation.

Determining reference ranges for immunological cells of healthy indigenous individuals from a region in Brazil

ABSTRACT Objective The establishment of reference values for a subset of leukocytes is common in clinical practice, and ethnic variations are strongly associated with disease development. In Brazil, indigenous people are vulnerable to infections, and few studies have described the health and disease conditions of this population. This study aimed to provide reference values for immunological cell subsets in indigenous Brazilians living in the state of Mato Grosso do Sul. Methods Flow cytometry and 4-color combinations of monoclonal antibodies were used to characterize cells. A total of 115 healthy adults, mostly females (72%), were included in the study. The results are presented as mean and median (2.5%-97.5% percentiles) for T and B lymphocytes, CD4+ T cells, CD8+ T cells, Natural Killer cells, monocytes, and dendritic cells, providing an average immunological profile for the population in question. Results The relative medians of CD3+, CD4+, and CD8+ T cells were significantly higher in women than in men in a healthy indigenous population. Conclusion To our knowledge, cell reference data from indigenous Brazilians are unknown in the literature. The immune cell results presented in this pioneering study will contribute to the clinical and laboratory evaluation of the Brazilian indigenous population, especially given the important differences when compared with other Brazilian ethnic groups.

Humoral immunity is not altered in overweight pregnant Crioulo mares / Imunidade humoral não é alterada em éguas Crioulas gestantes com sobrepeso

Both pregnancy and obesity can influence significant changes in the immune system. On this basis, the present study proposes to evaluate the humoral immune response of overweight pregnant mares in response to a commercial vaccine. Thirty pregnant Crioulo mares were separated according to body condition score (BCS) into overweight (BCS≥7/9) or lean-control (BCS= 5-6/9). In each group, the animals were subdivided into vaccinated and controls. The mares were vaccinated against EHV-1 in two doses spaced 21 days apart and had their blood collected monthly, for five months, for antibody evaluation. Both vaccinated groups had an increase in specific neutralizing antibodies after the vaccine. However, after the second dose, there was no increase in antibodies in any of the groups. Vaccinated overweight and lean-control mares did not differ at any time point. Therefore, this study demonstrated that obesity does not influence the humoral immune response in pregnant Crioulo mares.(AU)

Tanto a gestação quanto a obesidade podem influenciar o desenvolvimento de alterações significativas no sistema imune, portanto, o presente estudo teve como objetivo avaliar a resposta imune humoral de éguas gestantes com sobrepeso em resposta a uma vacina comercial. Trinta éguas Crioulas gestantes foram separadas de acordo com o escore de condição corporal (ECC) em éguas com sobrepeso (ECC≥7/9) e éguas controles (ECC=5-6/9) e, ainda, em cada grupo, os animais também foram separados em vacinados e controles. As éguas foram vacinadas contra o EHV-1 em duas doses com intervalo de 21 dias, sendo realizadas coletas de sangue mensalmente durante cinco meses para avaliação de anticorpos neutralizantes. Ambos os grupos vacinados tiveram aumento de anticorpos neutralizantes específicos após a vacina, porém, após a segunda dose, não foi observado aumento de anticorpos em nenhum dos grupos. Nenhuma diferença foi observada entre éguas vacinadas com sobrepeso e as éguas controles em nenhum momento. Assim, este estudo demonstrou que a obesidade não é um fator que influencia a resposta imune humoral de éguas Crioulas gestantes.(AU)

Does enteral nutrition through a percutaneous endoscopic gastrostomy, attenuate Helicobacter pylori colonization?: is it worth mentioning?

SUMMARY OBJECTIVE: In patients who experience difficulties in oral feeding, alimentary intake can be supported by creating direct access into the stomach through a percutaneous endoscopic gastrostomy. The present study purposed to compare naïve and exchanged percutaneous endoscopic gastrostomy tubes in terms of Helicobacter pylori infection and other clinical characteristics. METHODS: A total of 96 cases who underwent naïve or exchanged percutaneous endoscopic gastrostomy procedures with various indications were incorporated into the study. The patients' demographic data, such as age and gender, etiology of percutaneous endoscopic gastrostomy, anti-HBs status, Helicobacter pylori status, the presence of atrophy and intestinal metaplasia, biochemical parameters, and lipid profiles, had been analyzed. In addition, the anti-HCV and anti-HIV statuses had also been evaluated. RESULTS: The most common indication for percutaneous endoscopic gastrostomy placement was dementia in 26 (27.08%) cases (p=0.033). The presence of Helicobacter pylori positivity was significantly lower in the exchange group compared to the naïve group (p=0.022). Total protein, albumin, and lymphocyte levels were significantly higher in the exchange group compared to the naïve group (both p=0.001), and the mean calcium, hemoglobin, and hematocrit levels were statistically significantly higher in the exchange group (p<0.001). CONCLUSION: Preliminary outcomes of the present study revealed that enteral nutrition attenuates the incidence of Helicobacter pylori infection. Considering the acute-phase reactant, the significantly lower ferritin values in the exchange group suggest that there is no active inflammatory process in the patients and that immunity is sufficient.

Traditional Chinese Medicine Treatment, Gua Sha, can Induce Subtle Molecular Changes in Gene Expression / 生物医学与环境科学（英文）

OBJECTIVE@#Here, we explored molecular changes that could potentially mediate healing effects of Gua Sha - a method employed by the Chinese traditional medicine with proven track records of safe and efficient applications dating back to ancient times as well as support from randomized controlled trials performed by modern medical studies - yet remaining almost entirely unexplored by the modern-day high-throughput methods of the -omics sciences.@*METHODS@#We investigated transcriptome changes occurring shortly after Gua Sha treatment in the whole blood of healthy volunteers using bulk RNA-seq analysis. We applied various analytical tools to identify genes with consistent expression changes in multiple individuals in response to Gua Sha and their networks.@*RESULTS@#We found that while the changes were very subtle and individual-specific, we could identify consistent upregulation of three histone genes. Further analysis of the potential regulatory networks of these histone genes revealed the enrichment of functions involved in the immune response and inflammation.@*CONCLUSION@#The significance of these results in the context of potential effects of Gua Sha and the next steps in exploring the molecular mechanisms of action of this technique are discussed.

The role of γ-aminobutyric acid in tumor immunity / 药学学报

italic>γ-Aminobutyric acid (GABA) is a crucial inhibitory neurotransmitter found in various cells in the human body. While the GABAergic system is typically associated with the nervous system, recent research has revealed that immune cells and tumor cells also express components of this system. In the tumor microenvironment (TME), GABA is secreted to act extracellularly on other cells. GABA is metabolized via the GABA shunt and is involved in the tricarboxylic acid (TCA) cycle by generating succinate, which can provide energy for tumor cells. Activation of GABA receptors (GABARs) is a major pathway through which GABA participates in the regulation of antitumor immune responses. The activation of GABA type A receptors (GABAARs) can inhibit the activation and proliferation of T cells, elicit anti-inflammatory macrophages, and promote tumor cell growth and migration, while activation of GABA type B receptors (GABABRs) is generally considered to inhibit cancer cell migration and induce cancer cell apoptosis. In general, receptor activation inhibits immune cells, but the effect on tumor cells varies. Additionally, the downregulation of the expression levels of GABA transporters (GATs) is involved in tumor progression. Although antagonists of GABA metabolism and drugs that act on GABA receptors are considered therapeutic drugs for tumors, there have been few clinical studies conducted on them.

Efficacy of immune checkpoint inhibitors combined with concurrent chemotherapy in treatment of non-small cell lung cancer and its effect on levels of tumor markers and immune cells of patients / 肿瘤研究与临床

Objective:To investigate the effect of immune checkpoint inhibitors combined with concurrent chemotherapy for non-small cell lung cancer (NSCLC) and the effect of this regimen on serum levels of tumor marker and immune cells of patients.Methods:The clinical data of 60 NSCLC patients in Xuzhou Cancer Hospital from February 2020 to February 2022 were retrospectively analyzed, and they were divided into chemotherapy combined with immune checkpoint inhibitor treatment group (combination treatment group) and conventional chemotherapy group by treatment methods, with 30 cases in each group. Before treatment and 6 weeks after treatment, the patients' serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), vascular endothelial growth factor (VEGF), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) were detected by chemiluminescence immunoassay, and the levels of serum tumorous M2 pyruvate kinase (TuM2-PK) and fatty acid synthase (FAS) were detected by double-antibody sandwich enzyme-linked immunosorbent assay. The levels of T cell subsets were measured by flow cytometry, and the quality of life of patients was evaluated according to the World Health Organization quality of life scale brief version (WHOQOL-BREF). The clinical efficacy, tumor markers levels, immune cells levels, quality of life and adverse reactions were compared between the two groups.Results:The overall effective rate of patients in the combination treatment group was 46.67% (14/30), which was higher than 20.00% (6/30) in the conventional chemotherapy group ( χ2 = 4.80, P = 0.029). The differences in serum CEA, CA125, VEGF, CYFRA21-1, TuM2-PK, FAS levels and the proportions of CD3 +, CD4 +, CD8 + T cells and WHOQOL-BREF scores between the two groups before treatment were not statistically significant (all P > 0.05); the levels of CEA, CA125, VEGF, CYFRA21-1, TuM2-PK, FAS and the proportion of CD8 + T cells at 6 weeks after treatment were lower than those before treatment in both groups (all P < 0.05), and the proportions of CD3 + and CD4 + T cells and WHOQOL-BREF scores were higher than those before treatment (all P < 0.05); the levels CEA, CA125, VEGF, CYFRA21-1, TuM2-PK and the proportions of CD8 + T cells in the combination treatment group at 6 weeks after treatment were higher than those in the conventional chemotherapy group at 6 weeks after treatment (all P < 0.001), and the proportions of CD3 + and CD4 + T cells and WHOQOL-BREF scores were higher than those in the conventional chemotherapy group at 6 weeks after treatment (all P < 0.05). The differences in the incidence of gastrointestinal reactions, alopecia, leukopenia, thrombocytopenia, and liver and kidney function impairment between the two groups were not statistically significant (all P > 0.05). Conclusions:Immune checkpoint inhibitors combined with chemotherapy in NSCLC patients are more effective than conventional chemotherapy, and the combined treatment can more effectively reduce the serum tumor marker levels of patients and enhance the anti-tumor immune effect, with the adverse reactions comparable to conventional chemotherapy.

Value of serum IgG4 and IgG4/IgG ratio in differential diagnosis of autoimmune diseases / 中国基层医药

Objective:To investigate the value of immunoglobulin G4 (IgG4) and IgG4/ immunoglobulin G (IgG) ratio in the differential diagnosis of IgG4-related diseases (IgG4-RD) and other autoimmune diseases.Methods:A total of 35 patients with IgG4-RD and 937 patients with autoimmune diseases who received treatment in Beijing Hospital from January 2021 to July 2022, and 200 subjects who concurrently underwent health checkups in the same hospital were included in this study. The IMMAGE 800 and BN II automatic special protein analyzers were used to detect IgG and IgG4. The receiver operating characteristic (ROC) curve of IgG4 and IgG4/IgG ratio was plotted.Results:Serum IgG4 level and IgG4/IgG ratio in the IgG4-RD group were 2.83 (2.01, 5.07) g/L and 25% (18%, 43%) respectively, which were higher than 0.35 (0.16, 0.72) g/L, 3% (1%, 6%) in the autoimmune disease group and 0.27 (0.14, 0.49) g/L, 2% (1%, 4%) in the healthy control group ( U = 795.50, 82.50, 1 744.50, 205.50, all P < 0.001). Taking IgG4 ≥ 1.35 g/L as the standard, patients with IgG4 ≥ 1.35 g/L in the three groups were screened out. There was a statistically significant difference in IgG4/IgG ratio between the IgG4-RD group and the non-IgG4-RD group ( U = 453.50, P < 0.001). The ROC curve of IgG4 and IgG4/IgG ratio showed that when IgG4 was 1.47 g/L, the sensitivity was 91.7%, the specificity was 83.5%, and the area under the ROC curve was 0.96. When IgG4/IgG was 12.5%, the sensitivity was 91.4%, the specificity was 85%, and the area under the ROC curve was 0.96. Taking IgG4 ≥ 1.47 g/L and IgG4/IgG ≥ 12.5% as the diagnostic criteria of IgG4-RD, the sensitivity was 94.3%, the specificity was 85.9%, and the area under the ROC curve was 0.96, which were higher than the sensitivity (87.2%) and diagnostic specificity (82.6%) provided by IgG4 alone. Conclusion:Because non-IgG4-RD diseases can also have the phenomenon of increased IgG4, when IgG4 ≥ 1.47 g/L is taken as the diagnostic criteria, its diagnostic sensitivity and specificity are the highest. Combined detection of IgG4 and IgG4/IgG ratio can increase the diagnostic efficacy of IgG4-RD.